The aim of cardiopulmonary bypass is the maintenance of a sufficient whole body perfusion and gas exchange during open or closed heart surgery procedure (coronary artery bypass grafting, valve repair and replacement, surgical intervention on the ascending aorta and/or aortic arch, repair of congenital malformations, and finally implantation of ventricular assist devices or cardiac transplantation). The main components of cardiopulmonary bypass are the pump that supplies the circulation and the oxygenator that regulates gas exchange. However, even though this technology has been extensively developed and improved over the last decades, one of the major drawbacks—which is the fact that blood has to flow through tubing systems with foreign surfaces—persists so far. Nevertheless, interesting innovations have been made more recently in order to better control the side-effects that culminate into a major activation of the coagulation and inflammatory systems: among them, miniaturization of the circuits, together with reduction of the priming volume and a simplified cardioplegia concept. All of these lead to a significant decrease of hemodilution and thereby a significant reduction of volume overload during surgery. In this brief review we will present some of these most interesting topics around minimized circuits and the simplified low-volume cardioplegia and discuss their potential benefits on the clinical outcome.